borneol | 507-70-0

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 消毒防腐药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: borneol
• 英文别名: isoborneol；endo-borneol；1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
• CAS: 507-70-0
• 化学式: C₁₀H₁₈O
• mdl: MFCD00064162
• 分子量: 154.252
• InChiKey: DTGKSKDOIYIVQL-UHFFFAOYSA-N

物化性质

• 熔点：
  206-209 °C
• 比旋光度：
  -0.5～+0.5゜(20℃/D)(c=5,C2H5OH)
• 沸点：
  210 °C(lit.)
• 密度：
  1.011
• 蒸气密度：
  5.31 (vs air)
• 闪点：
  150 °F
• 溶解度：
  DMSO:30.0(最大浓度 mg/mL);194.49(最大浓度 mM)乙醇:30.0(最大浓度 mg/mL);194.49(最大浓度 mM)
• LogP：
  3.6 at 20℃
• 物理描述：
  Borneol appears as a white colored lump-solid with a sharp camphor-like odor. Burns readily. Slightly denser than water and insoluble in water. Used to make perfumes.
• 颜色/状态：
  White to off-white crystals
• 气味：
  Piney, camphor-like odor
• 味道：
  Burning taste somewhat reminiscent of mint
• 蒸汽压力：
  5.02X10-2 mm Hg at 25 °C
• 稳定性/保质期：
  1. 按照规格使用和贮存，不会发生分解，并避免与氧化物接触。
  2. 它存在于烟叶中。
  3. （+）-龙脑天然存在于薰衣草油、香紫苏油、迷迭香油以及某些樟脑油中。（-）-龙脑则存在于芫荽油、香茅油、松节油等精油中。
  4. 有一定的毒性、刺激性和过敏性反应。
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 气味阈值：
  Detection: 2.5 to 16 ppb
• 保留指数：
  1698;1604

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

毒理性

• 毒性总结

识别和使用：冰片是一种固体。它被用作香料，并作为药物使用，包括传统中医。人类暴露和毒性：冰片不会引起皮肤过敏。其毒性实质上与樟脑相似。人类外周血淋巴细胞在DMSO中暴露于不同浓度的l-冰片，浓度高达600微克/毫升，持续4小时，有和无代谢激活以及24小时无代谢激活。在研究的条件下，l-冰片被认为不具有致裂变性。动物研究：与樟脑类似，实验室动物对冰片的毒性似乎比人类要小得多。冰片增加了大鼠口服处理7天后CYP2D的活性。冰片在小鼠中已被评估其镇痛和抗炎活性。冰片在爪子舔舐的早期和晚期显著减少了痛觉行为，并减少了小鼠的扭动反射。当进行热板测试时，高剂量的冰片产生了痛觉行为的抑制。此外，冰片处理的小鼠减少了角叉菜胶诱导的白细胞迁移到腹腔。冰片的致突变潜力在Ames试验中通过使用鼠伤寒沙门氏菌TA1535、TA1537、TA1538、TA98和TA100菌株，在存在和不存在代谢激活的情况下，用冰片以高达5000微克/平板的浓度处理进行了评估。其他研究证实了在鼠伤寒沙门氏菌TA98和TA100菌株中缺乏致突变潜力。在研究的条件下，冰片被认为在细菌中不具有致突变性。

IDENTIFICATION AND USE: Borneol is a solid. It is used as a flavoring, and as a medication, including traditional Chinese medicine. HUMAN EXPOSURE AND TOXICITY: Borneol does not present a concern for skin sensitization. Toxicity is essentially indistinguishable from that of camphor. Human peripheral blood lymphocytes were exposed to varying concentrations of l-borneol in DMSO up to 600 ug/mL for 4 hr, with and without metabolic activation and 24 hr without metabolic activation. Under the conditions of the study, l-borneol was considered non-clastogenic. ANIMAL STUDIES: As with camphor, laboratory animals appear to be much less susceptible to borneol toxicity than man. Borneol increased the activity of CYP2D in rats orally treated by borneol for 7 days. Borneol has been evaluated for antinociceptive and anti-inflammatory activities in mice. Borneol produced a significant reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice. When the hot plate test was conducted, borneol (in higher dose) produced an inhibition of the nociceptive behavior. Additionally, borneol-treated mice had reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. The mutagenic potential of borneol was assessed in an Ames test with Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 treated with borneol at concentrations up to 5000 ug/ plate in the presence and absence of metabolic activation. Other studies confirming a lack of mutagenic potential in S. typhimurium strains TA98 and TA100 have been published. Under the conditions of the study, borneol is considered not mutagenic in bacteria.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：异冰片是一种白色固体。它被用作食品和饮料中的香料成分。它也用于香水制造和化学酯的制备。人体研究：在一项人体最大量测试中，没有观察到10%异冰片在凡士林中引起的敏感性反应。在0.016%至0.08%的浓度范围内，异冰片对人细胞系测试时没有表现出显著的细胞毒性。动物研究：在0.016%至0.08%的浓度范围内，异冰片对猴细胞系测试时没有表现出显著的细胞毒性。交叉参考化学品l-冰片和异冰片醋酸酯进行了遗传毒性、重复剂量毒性、发育和生殖毒性的评估。在针对大鼠进行的异冰片醋酸酯13周亚慢性毒性研究中，根据增加的尿细胞排泄，确定无观察到效应水平（NOEL）为15 mg/kg/天。在亲代生殖毒性的无观察到有害效应水平（NOAEL）确定为异冰片醋酸酯300 mg/kg/天。l-冰片在Ames试验中不是致突变剂。异冰片在Bluescreen分析中评估了其遗传毒性潜力，发现在有和没有代谢激活的情况下对遗传毒性和细胞毒性均为阴性。

IDENTIFICATION AND USE: Isoborneol is a white solid. It is used as a flavor ingredient in food and beverages. It is also used in perfumery and in preparation of chemical esters.HUMAN STUDIES: In a human maximization test, no reactions indicative of sensitization were observed with 10% isoborneol in petrolatum. Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human cell lines. ANIMAL STUDIES: Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against monkey cell lines. Read across chemicals l-borneol and isobornyl acetate were evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity. In the13-week subchronic toxicity study for isobornyl acetate conducted in rats the NOEL was determined to be 15 mg/kg/day, based on increased urinary cell excretion.The NOAEL for reproductive toxicity in the parental generation was determined to be 300 mg/kg/day for isobornyl acetate. l-borneol was not mutagenic in the Ames test. Isoborneol, was assessed for genotoxic potential in the Bluescreen assay and was found negative for genotoxicity and cytotoxicity in the presence and absence of metabolic activation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

为了开发一种气相色谱-火焰离子化检测法（GC-FID）来测定冰片在小鼠组织中的浓度，并研究静脉注射和鼻腔给药后冰片的组织分布，收集了给予30.0 mg/kg冰片剂量后1、3、5、10、20、30、60、90、120分钟的小鼠大脑、心脏、肝脏、脾脏、肺和肾脏。用乙酸乙酯提取组织中的药物，并通过气相色谱检测冰片浓度，以十八烷为内标。校准曲线显示出良好的线性关系。提取回收率、日间和日内精密度以及稳定性符合生物样本分析的要求。冰片主要分布在大多数组织中，心脏、大脑和肾脏中较多，肝脏、脾脏和肺中较少。建立的GC-FID方法适用于组织中冰片含量的测定。在小鼠静脉注射和鼻腔给药后，冰片主要分布在血液供应丰富的组织中。在鼻腔给药后，大脑组织显示出最高的靶向系数和靶向效果。

To develop a GC-FID method to determine borneol's concentration in mouse tissues, and to investigate the tissue distribution after intravenous and intranasal administrations of borneol, mouse brains, hearts, livers, spleens, lungs and kidneys were collected at 1, 3, 5, 10, 20, 30, 60, 90, 120 min after administration of borneol with the dose of 30.0 mg/kg. The drug in tissues was extracted with ethyl acetate, and borneol's concentration detected by GC, with octadecane as the internal standard. The calibration curve showed a good linear relationship. Extraction recoveries, inter-day and intra-day precisions and stability were in conformity with the analytical requirements of biological samples. Borneol was mainly distributed in most tissues, more in heart, brain and kidney, and less in liver, spleen and lung. The established GC-FID method is applicable for content determination of borneol in tissues. After intravenous and intranasal administrations in mice, borneol is mainly distributed in abundant blood-supply tissues. After intranasal administration, brain tissues showed the highest target coefficient and target effectiveness.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了理解静脉注射、鼻腔给药或口服给药后血液和大脑的药物动力学，并探讨鼻腔给药的优越性和可行性，开发了一种带有火焰离子化检测（FID）的简单气相色谱（GC）方法，用于定量测定冰片。在给小鼠静脉注射、鼻腔给药或口服给药30.0 mg/kg冰片后，分别于1、3、5、10、20、30、60、90和120分钟收集血液样本和大脑。样品前处理是通过使用辛烷内标溶液的液-液萃取来进行的。药代动力学参数是通过计算机软件计算得出的。血浆和大脑中冰片的校准曲线分别在0.11-84.24 ug/mL和0.16-63.18 ug/g范围内呈线性。方法回收率和提取回收率均在85%-115%范围内。血浆和大脑样本的日内和日间变异性均小于或等于5.00%相对标准偏差（RSD）。鼻腔给药和口服给药的绝对生物利用度F分别为90.68%和42.99%。鼻腔给药和口服给药的相对脑靶向系数Re分别为68.37%和38.40%。所开发的GC-FID方法可用于测定和药代动力学研究。注射给药的冰片分布和代谢速度快，无需吸收过程。口服给药的冰片分布较慢，绝对生物利用度最低。冰片的鼻腔给药能迅速吸收进入血液和大脑，使用方便，安全性大于感染，这使得它值得作为治疗脑病的给药途径进一步开发。

... In order to understand the blood and brain pharmacokinetics after intravenous, intranasal, or oral administration and to investigate the superiority and feasibility of intranasal administration, a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol. Blood samples and brain were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 min after intravenous, intranasal, or oral administration of borneol at a dosage of 30.0 mg/kg. Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane. The pharmacokinetic parameters were calculated /using computer software/. The calibration curves were linear in the range of 0.11-84.24 ug/mL and 0.16-63.18 ug/g for borneol in plasma and brain, respectively. The methodological and extraction recoveries were both in the range of 85%-115%. The intra-day and inter-day variabilities for plasma and brain samples were </= 5.00% relative standard deviation (RSD). The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%. The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%. The GC-FID method developed could be applied to determination and pharmacokinetic study. The borneol from injection was distributed and metabolized fast without absorption process. The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability. Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection, which makes it worthy of further development as an administration route for encephalopathy treatment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这项工作的目的是研究冰片的原位和活体鼻腔吸收。应用了一种新颖的单次通过原位鼻腔灌注技术来检查大鼠鼻腔吸收冰片的速率和程度。研究了灌注速率、pH值和药物浓度等实验条件。原位实验显示，冰片的鼻腔吸收不依赖于药物浓度，并且符合一级过程。吸收速率常数Ka随着灌注速度的增加而变化。在鼻咽腔的生理条件下，冰片在pH范围内和pH值条件下被很好地吸收。在大鼠中进行了冰片吸收的活体研究，并比较了鼻腔内给药（in）与静脉给药（iv）的药代动力学参数。冰片鼻腔内给药的生物利用度为90.82%，达到最大浓度的时间Tmax为10分钟。平均滞留时间MRT分别为262.55 +/- 67.35分钟和204.22 +/- 14.50分钟，分别对应于鼻腔内给药和静脉给药。结果表明，冰片可以通过大鼠鼻腔内给药被迅速且彻底吸收。

The aim of this work was to study the in situ and in vivo nasal absorption of borneol. A novel single pass in situ nasal perfusion technique was applied to examine the rate and extent of nasal absorption of borneol by rats. Experimental conditions, such as perfusion rate, pH and drug concentration, were investigated. The in situ experiments showed that the nasal absorption of borneol was not dependent on drug concentration, and fitted a first order process. The absorption rate constant, Ka, influenced with an increase in perfusion speed. The borneol was well absorbed in the conditions of the nasal cavity within the pH range and pH value of physiological conditions. In vivo studies of borneol absorption were carried out in rats and the pharmacokinetics parameters of intranasal (in) was compared with intravenous (iv) administration. The bioavailabilities of borneol was 90.82% for i.n. while Tmax values were 10 min. MRT (Mean Residence Time) were 262.55 +/- 67.35 min and 204.22 +/- 14.50 min for in and iv methods, respectively. The results demonstrate that borneol could be absorbed promptly and thoroughly by in administration in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

先前的研究表明，冰片对中枢神经系统（CNS）具有双重作用，但机制尚不清楚。本研究的目的是阐明兴奋比率[兴奋性氨基酸（AAs）含量与抑制性氨基酸含量之比]与单次口服剂量后天然冰片含量的关系。小鼠通过口服摄入给予1.2 g/kg剂量的天然冰片（含98% D: -冰片）。在给药前和给药后0.083、0.167、0.25、0.333、0.5、0.75、1、1.5、2、2.5、3、4和5小时收集脑样本。通过GC-MS和HPLC-FLU分别测定小鼠脑中天然冰片的浓度和AA神经递质的含量。口服给药后，天然冰片迅速被吸收进入大脑，并在给药后5分钟可检测到。给药后1小时达到最大脑浓度（86.52微克/克）。天然冰片能够影响小鼠脑中AA神经递质的含量：L: -门冬氨酸在给药后0.083至1小时显著增加，L: -谷氨酸在给药后0.333小时显著增加并在1.5至5小时降低，γ-氨基丁酸在给药后0.167至5小时显著增加，而甘氨酸不受影响。兴奋比率是兴奋性AAs含量与抑制性AAs含量之比，反映了机体的兴奋或抑制状态。兴奋比率在给药后0.5小时暂时升高然后下降；在给药后1.5-5小时与给药前有显著差异。本研究表明，天然冰片能够影响AA神经递质的含量，兴奋比率的改变导致冰片对CNS的双重作用。

Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol after a single oral dose. Mice were administered a 1.2 g/kg dose of natural borneol (containing 98% D: -borneol) by oral ingestion. Brain samples were collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hr after administration. The brain concentration of natural borneol and contents of AA neurotransmitters in mice brain were determined by GC-MS and HPLC-FLU, respectively. After per oral application, natural borneol was absorbed rapidly into the brain and could be determined 5 min after dosing. The maximal brain concentration (86.52 ug/g) was reached after 1 hr post-dosing. Natural borneol could affect the contents of AA neurotransmitters in mice brain: L: -aspartic acid increased significantly from 0.083 to 1 hr after administration, L: -glutamic acid increased significantly at 0.333 hr and decreased from 1.5 to 5 hr, gamma-amino-N-butyric acid increased significantly from 0.167 to 5 hr, whereas glycine was not affected. The excitation ratio is the contents of excitatory AAs versus that of inhibitory AAs, which reflects the excitatory or inhibitory state of the body. The excitation ratio elevated transitorily and then declined 0.5 hr post-dosing; there were significant differences between 1.5-5 hr post-dose compared with pre-dose. The present study indicated that natural borneol could affect the contents of AA neurotransmitters, and the change in excitatory ratio led to borneol's double side effects on the CNS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

松节油、异冰片醇醋酸酯、柠檬烯、薄荷醇和α-松烯作为泡沫浴（Pinimenthol）成分的经皮吸收情况通过使用放射性标记成分在动物身上进行了测量。药代动力学测量显示，所有测试成分在经皮吸收开始后10分钟达到最大血药水平。没有发现任何成分有优先吸收的情况。经皮吸收10分钟后所有成分的血药水平与皮肤面积大小直接相关。

The percutaneous absorptions of camphene, isoborneol-acetate, limonene, menthol and alpha-pinene as constituents of a foam bath (Pinimenthol) were measured on animals using radioactively labeled ingredients. Pharmacokinetic measurements showed maximum blood levels for all tested ingredients 10 min after the onset of percutaneous absorption. None of the ingredients was preferentially absorbed. Blood levels of all ingredients after 10 min of percutaneous absorption were a direct function of the size of the skin area involved.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  4.1
• 危险品标志：
  F
• 安全说明：
  S16,S36/37
• 危险类别码：
  R22,R11
• WGK Germany：
  2
• 海关编码：
  2906199090
• 危险品运输编号：
  UN 1312
• 危险类别：
  4.1
• RTECS号：
  DT5095000
• 包装等级：
  III
• 储存条件：
  储存于阴凉、干燥、通风良好的库房，远离火种和热源，防止阳光直射。包装需密封，并与酸类及食用化学品分开存放，切忌混储。储存区域应备有合适的材料以处理泄漏物。

SDS

第一部分：化学品名称

化学品中文名称：	2-茨醇；冰片
化学品英文名称：	Borneol；2-Camphanol
中文俗名或商品名：
Synonyms：
CAS No.：	507-70-0
分子式：	C 10 Hl 8 O
分子量：	154.2

第二部分：成分/组成信息

纯化学品 混合物

化学品名称：2-茨醇；冰片

有害物成分 含量 CAS No.

第三部分：危险性概述

危险性类别：	第4．1类 易燃固体
侵入途径：	吸入 食入
健康危害：	吸收后有微毒，可能引起过敏反应，有刺激作用。接触后可引起头痛、恶心、呕吐及惊厥。
环境危害：
燃爆危险：	本品易燃，具刺激性，具致敏性。

第四部分：急救措施

皮肤接触：	脱去污染的衣着，用月巴皂水及清水彻底冲洗。
眼睛接触：	立即翻开上下眼睑，用流动清水冲洗15分钟。就医。
吸入：	脱离现场至空气新鲜处。就医。
食入：	误服者用水漱口，立即就医。

第五部分：消防措施

危险特性：	遇高热、明火或与氧化剂接触，有引起燃烧的危险。粉体与空气可形成爆炸性混合物，当达到一定的浓度时，遇火星会发生爆炸。
有害燃烧产物：	一氧化碳、二氧化碳。
灭火方法及灭火剂：	雾状水、二氧化碳、干粉、泡沫。
消防员的个体防护：	消防人员须佩戴防毒面具、穿全身消防服，在上风向灭火。
禁止使用的灭火剂：
闪点(℃)：	65
自燃温度(℃)：	引燃温度(℃)：无资料
爆炸下限[%(V/V)]：	无资料
爆炸上限[%(V/V)]：	无资料
最小点火能(mJ)：
爆燃点：
爆速：
最大燃爆压力(MPa)：
建规火险分级：

第六部分：泄漏应急处理

应急处理：

切断火源。戴好口罩和手套。用砂土、干燥石灰或苏打灰混合，收集运到空旷处焚烧。如大量泄漏，收集回收或无害处理后废弃。

第七部分：操作处置与储存

操作注意事项：	密闭操作，全面通风。操作人员必须经过专门培训，严格遵守操作规程。建议操作人员佩戴自吸过滤式防尘口罩，戴化学安全防护眼镜，穿防毒物渗透工作服，戴橡胶手套。远离火种、热源，工作场所严禁吸烟。使用防爆型的通风系统和设备。避免产生粉尘。避免与氧化剂接触。搬运时轻装轻卸，防止包装破损。配备相应品种和数量的消防器材及泄漏应急处理设备。倒空的容器可能残留有害物。
储存注意事项：	储存于阴凉、通风的库房。远离火种、热源。库温不超过32℃，相对湿度不超过80％。应与氧化剂分开存放，切忌混储。采用防爆型照明、通风设施。禁止使用易产生火花的机械设备和工具。储区应备有合适的材料收容泄漏物。

第八部分：接触控制/个体防护

最高容许浓度：	中 国 MAC：未制订标准前苏联 MAC：未制订标准美国TLV—TWA：未制订标准
监测方法：
工程控制：	生产过程密闭，全面通风。
呼吸系统防护：	可能接触其蒸气时，应该佩戴防毒面具。
眼睛防护：	可采用安全面罩。
身体防护：	穿防静电工作服。
手防护：	一般不需特殊防护。
其他防护：	工作现场严禁吸烟。保持良好的卫生习惯。

第九部分：理化特性

外观与性状：	白色、半透明结晶，有似樟脑气味，能升华。
pH：
熔点(℃)：	208(D)；204(L)
沸点(℃)：	212(D)；210(L)(104kPa)
相对密度(水=1)：	1．01(D，20℃)
相对蒸气密度(空气=1)：	5．3(D)
饱和蒸气压(kPa)：
燃烧热(kJ/mol)：
临界温度(℃)：
临界压力(MPa)：
辛醇/水分配系数的对数值：
闪点(℃)：	65
引燃温度(℃)：	引燃温度(℃)：无资料
爆炸上限%(V/V)：	无资料
爆炸下限%(V/V)：	无资料
分子式：	C 10 Hl 8 O
分子量：	154.2
蒸发速率：
粘性：
溶解性：	溶于醇、醚，微溶于水。
主要用途：	用于制造龙脑酯类、香料等。

第十部分：稳定性和反应活性

稳定性：	在常温常压下 稳定
禁配物：	强氧化剂。
避免接触的条件：
聚合危害：	不能出现
分解产物：	一氧化碳、二氧化碳。

第十一部分：毒理学资料

急性毒性：	属微毒类，有刺激性。 LD50：5800mg／kg(大鼠经口) LC50：
急性